News & Perspective
Drugs & Diseases
CME & Education
Academy
Video
Decision Point
Edition: English

Medscape

English
Deutsch
Español
Français
Português
UKNew

Univadis

Sign Up It's Free!
English Edition

Medscape

Univadis

    X
    Univadis from Medscape

    No Results

      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Gastroenterology

      Hepatitis C Medication

      Updated: Oct 07, 2019
      • Author: Vinod K Dhawan, MD, FACP, FRCPC, FIDSA; Chief Editor: BS Anand, MD  more...
      • Print
      Medication

      Medication Summary

      The treatment of chronic hepatitis C has evolved rapidly. In the past the backbone of treatment for chronic hepatitis C virus (HCV) infection regardless of genotype was a combination therapy with injectable pegylated interferon-alfa (PEG-IFNa) plus oral ribavirin. Because it has the poorest safety profile of all the HCV antivirals, with few exceptions, PEG-IFN is no longer recommended in combination regimens. Ribavirin continues to be used in combination with sofosbuvir alone or other combinations.

      The direct-acting antiviral agents (DAAs), first introduced in 2011, offered enhanced efficacy when combined with both PEG-IFN and ribavirin, particularly for genotype 1 infections. The first protease inhibitors, boceprevir and telaprevir, are no longer available for use in the United States and have been supplanted by antivirals with greater efficacy and improved safety profiles.

      There are three classes of approved DAAs: NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors (nonnucleoside inhibitors and nucleotide inhibitors). The particular combination of antivirals is determined by genotype. Several novel agents are only available as a fixed-dose combination. The following combinations are currently available:

      • Ledipasvir/sofosbuvir (Harvoni)
      • Elbasvir/grazoprevir (Zepatier)
      • Ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak)
      • Ombitasvir/paritaprevir/ritonavir (Technivie)
      • Glecaprevir/pibrentasvir (Mavyret)
      • Sofosbuvir/velpatasvir/voxilaprevir (Vosevi)
      • Sofosbuvir/velpatasvir (Epclusa): Combination therapy is required because monotherapy with either agent is not efficacious.

      For patients with chronic HCV infection and chronic kidney disease (CKD) stage 1, 2, or 3, the following drug regimens do not require dose adjustments [9] :

      • Simeprevir 150 mg
      • Sofosbuvir 400 mg
      • Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg)
      • Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)
      • Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)
      • Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)
      • Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100 mg)

      Although quite effective, regimens for the treatment of hepatitis C remain very expensive. In a study of treatment-naïve US veterans with genotype 1 HCV, ombitasvir-based therapy was considered to be the most economically efficient strategy. [130]

      Next:

      HCV Protease Inhibitors

      Class Summary

      These agents interfere with HCV replication by inhibiting a key viral enzyme, NS3/4A serine protease.

      Previous
      Next:

      HCV Polymerase Inhibitors

      Class Summary

      HCV NS5B polymerase plays an essential role in HCV replication.

      Sofosbuvir (Sovaldi)

      Sofosbuvir is a NS5B polymerase inhibitor that results in suppression of HCV replication and interrupts HCV life cycle. It is indicated for the treatment of CHC infection genotypes 1, 2, 3, and 4 as part of a combination antiviral regimen, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) to prevent HCV recurrence and those with HCV/HIV-1 coinfection.

      Previous
      Next:

      HCV NS5A Inhibitors

      Class Summary

      NS5A is integral for HCV RNA viral replication.

      Previous
      Next:

      Combination Products

      Class Summary

      Several combination products have been approved and additional ones are being investigated to provide all oral regimens with high degrees of efficacy.

      Ledipasvir/sofosbuvir (Harvoni)

      Ledipasvir inhibits HCV NS5A protein, which is required for viral replication. Sofosbuvir is an inhibitor of HCV NS5B RNA-dependent polymerase. The oral combination is indicated for treatment of adults with chronic hepatitis C infection with genotype 1, 4, 5, or 6. Duration of therapy ranges from 8 to 24 weeks and depends on if the patient is treatment-naïve or experienced, and if cirrhosis is evident.

      Ombitasvir/paritaprevir/ritonavir & dasabuvir (Viekira Pak)

      This product is indicated for the treatment of chronic HCV genotype 1 infection, including patients with compensated cirrhosis; may be used for patients with HCV/HIV-1 coinfection. It is used in combination with ribavirin in certain patient populations (ie, genotype 1a, with or without cirrhosis; genotype 1b, with cirrhosis). Ombitasvir inhibits HCV NS5A, which is required for viral replication. Paritaprevir is a NS3/4A serine protease inhibitor. NS3/4A protease is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. Ritonavir is a protease inhibitor that is used as a "boosting agent" to increase paritaprevir serum levels. Dasabuvir is a nonnucleoside NS5B RNA-dependent polymerase inhibitor. It's inhibition, in turn, suppresses viral replication.

      Ombitasvir/paritaprevir/ritonavir (Technivie)

      Ombitasvir/paritaprevir/ritonavir is indicated in combination with ribavirin for genotype 4 chronic HCV infection without cirrhosis. Ombitasvir inhibits HCV NS5A, which is required for viral replication. Paritaprevir is a NS3/4A serine protease inhibitor. NS3/4A protease is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. Ritonavir is a protease inhibitor that is used as a "boosting agent" to increase paritaprevir serum levels.

      Elbasvir/grazoprevir (Zepatier)

      Elbasvir is an inhibitor of HCV NS5A, which is essential for viral RNA replication and virion assembly. Grazoprevir is an inhibitor of HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication. It is indicated with or without ribavirin for the treatment of adults with chronic HCV genotypes 1 or 4 infection.

      Glecaprevir/pibrentasvir (Mavyret)

      Combination of glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor). Glecaprevir/pibrentasvir is indicated in treatment-naïve patients aged 12 years and older or weighing at least 45 kg with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). It also is indicated in patients aged 12 years and older or weighing at least 45 kg with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both. An 8-week regimen is approved for treatment-naïve patients with any genotype and for treatment-experienced patients with genotypes 1, 2, 4, 5, or 6 who had prior treatment with peginterferon, ribavirin, and/or sofosbuvir.

      Sofosbuvir/velpatasvir (Epclusa)

      Combination of sofosbuvir (NS5B RNA-dependent polymerase) and velpatasvir (pangenotypic NS5A inhibitor). It is indicated for adults with chronic hepatitis C virus (HCV) infection genotypes 1, 2, 3, 4, 5, or 6.

      Sofosbuvir/velpatasvir/voxilaprevir (Vosevi)

      Combination of sofosbuvir (NS5B RNA-dependent polymerase), velpatasvir (pangenotypic NS5A inhibitor), and voxilaprevir (pangenotypic NS3/4A protease inhibitor). It is indicated for retreatment of chronic hepatitis C virus (HCV) infection in adults with genotype 1, 2, 3, 4, 5, or 6 previously treated with an NS5A inhibitor-containing regimen, or with genotype 1a or 3 previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor.

      Previous
      Next:

      Interferons and ribavirin

      Class Summary

      Interferons are naturally produced proteins with antiviral, antitumoral, and immunomodulatory actions. Interferons alfa, beta, and gamma may be given topically, systemically, and intralesionally. Interferons are immunomodulators that may shorten the clinical course, prevent complications, prevent latent and/or subsequent recurrences, decrease transmission, and eliminate established latency.

      Interferon alfa-2b (Intron-A)

      IFN alfa-2b is a protein product manufactured by recombinant DNA technology. The adult dosage is 3 million units subcutaneously (SC) 3 times weekly. Modulation of host immune response by IFN may play an important role in the treatment of viral diseases.

      Peginterferon alfa-2b (PEG-Intron, Sylatron)

      PEG-IFN consists of IFN alfa-2b attached to a single 12-kd PEG chain. It is excreted by the kidneys. PEG-IFN has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified IFN, which permits more convenient once-weekly dosing and significantly improves the quality of life for patients. The adult dose is 1.5 mcg/kg SC.

      Pegylated interferon alfa-2a (Pegasys)

      PEG-IFN alfa-2a consists of IFN alfa-2a attached to a 40-kd branched PEG molecule. It is predominantly metabolized by the liver. The adult dosage is 180 mcg/kg SC once weekly.

      Ribavirin (Rebetol, Virazole, Copegus, Moderiba, Ribasphere)

      Ribavirin is an antiviral nucleoside analogue. Its chemical name is D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. Given alone, ribavirin has little effect on the course of hepatitis C. Given with IFN, it significantly augments the rate of sustained virologic response. The adult dosage is 10.6 mg/kg orally once daily or in 2 divided doses.

      Previous
      Next:

      Thrombopoietin-Receptor Agonists

      Class Summary

      These agents directly stimulate bone marrow platelet production to provide stable platelet counts to allow therapy with interferons.

      Eltrombopag (Promacta)

      Oral thrombopoietin (TPO) receptor agonist. Interacts with transmembrane domain of human TPO receptor and induces megakaryocyte proliferation and differentiation from bone marrow progenitor cells. This agent is indicated for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.

      Previous
      Questions
       
       
      Media Gallery
      of 48
      Find Us On
      About
      About Medscape Privacy Policy Editorial Policy Cookies Terms of Use Advertising Policy Help Center
      Membership
      Become a Member About You Professional Information Newsletters & Alerts Market Research
      App
      Medscape
      WebMD Network
      Medscape Live Events WebMD MedicineNet eMedicineHealth RxList WebMD Corporate Medscape UK
      Editions
      English Deutsch Español Français Português UK
      All material on this website is protected by copyright, Copyright © 1994-2023 by WebMD LLC. This website also contains material copyrighted by 3rd parties.